Patients with metastatic or unresectable, recurrent HNSCC
Conditions
Sponsors
Merck Sharp & Dohme Corp., a subsidiary of Merck &Co.,Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Has histologically or cytologically confirmed diagnosis of metastatic or unresectable,recurrent HNSCC that is considered incurable by local therapies. Has not had prior systemic therapy administered in the recurrent or metastatic setting. Systemic therapy which was completed more than 6 months prior to signing consent, if given as part of multimodal treatment for locally advanced disease, is allowed. The eligible primary tumor must be located in oropharynx, oral cavity, hypopharynx, or larynx. Participants may not have a primary tumor site of nasopharynx (any histology). 2. Has tumor PD-L1 expression of CPS =1. 3. Has at least 1 measurable lesion which is amenable to injection. IT injection for cutaneous lesions may be performed via visual inspection. IT injection for subcutaneous lesions may be performed via ultrasound guidance or via palpation. This injectable lesion must be measurable and meet one of the following criteria: A cutaneous or subcutaneous lesion =1 cm in longest diameter for solid tumors, or =1.5 cm in short axis for a nodal lesion in solid tumor subjects. The longest diameter for an injectable lesion must be =10 cm for both solid tumors and nodal lesions in solid tumor subjects. Multiple coalescing, superficial lesions which in aggregate have a longest diameter of =1 cm and =10 cm. 4. Has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 5. Demonstrates adequate organ function 6. Has results from testing of HPV status for oropharyngeal cancer defined as p16 IHC testing using CINtec® p16 Histology assay and a 70% cutoff point (please see the Procedures Manual for details). If HPV status was previously tested, then no additional testing is required. 7. Is male or female, from 18 years to unlimited years of age inclusive, at the time of signing the informed consent. 8. Male participants of reproductive potential must agree to use a highly effective method of contraception during sexual contact with females of childbearing potential starting with the first dose of study medication through 120 days after the last dose of study therapy. 9. Female participants of childbearing potential must be willing to use a highly effective method of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after last dose of study medication . Participants of childbearing potential are those who have not been surgically sterilized or have not been free of menses for >1 year. 10. Female participants of childbearing potential must have a negative urine or serum pregnancy test at screening and again within 72 hours prior to receiving the first dose of study treatment. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. The serum pregnancy test must be negative for the participant to be eligible. 11. Has voluntarily agreed to participate by giving written informed consent. The participant may also provide consent for Future Biomedical Research. However, the participant may participate in the main trial without participating in Future Biomedical Research. 12. HIV-infected participants must meet these additional criteria: a) Have HIV-1 infection documented by using any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry (Day 1). HIV-1 infection is to be confirmed by using a licensed Western blot or a second antibody test by a meth
Exclusion criteria
Exclusion criteria: 1.Has disease that is suitable for local therapy administered with curative intent 2. Has progressive disease within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC 3. Has had chemotherapy or biological cancer therapy in the recurrent or metastatic setting for the treatment of HNSCC 4. Has had radiation therapy within 2 weeks prior to randomization or subject has not fully recovered from adverse events due to a previously administered treatment 5. Is expected to require any other form of antineoplastic therapy while on study 6. Has a history of a second malignancy, unless potentially curative treatment has been completed, with no evidence of malignancy for at least 2 years 7. Has clinically active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain or meningeal metastases may participate and be eligible for treatment provided they are stable and asymptomatic, have no evidence of new or enlarging brain metastases, are evaluated within 4 weeks prior to first study intervention administration, and are off immunosuppressive doses of systemic steroids at least 2 weeks prior to enrolment 8. Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy. Replacement therapy, such as thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, is not considered a form of systemic treatment and is allowed. Use of nonsystemic steroids is permitted 9. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. Corticosteroid use as premedication for allergic reactions is allowed 10. Has had an allogenic tissue/solid organ transplant 11. Has a history of vasculitis 12. Has a history of interstitial lung disease 13. Has an active infection requiring systemic therapy 14. Has a known history of active tuberculosis 15. Has a history of pneumonitis that required steroids or current pneumonitis 16. Has had a severe hypersensitivity reaction to treatment a monoclonal antibody/component of the study intervention 17. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study in the opinion of the treating investigator 18. Participants with known Hepatitis B or C infections or known to be positive for HBsAg/HBV DNA or Hepatitis C Antibody or RNA. 19. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PDL2 agent or if the patient has previously participated in Merck MK-3475 clinical trials 20. HIV infected participants who have had an HIV-related opportunistic infection within 6 months 21. HIV infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease 22. Has known psychiatric or substance abuse disorders that would interfere with the participant's ability to cooperate with the requirements of the study 23. Is pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of study intervention 24. Has not fully recovered from any effects of major surgery without significant detectable infection. Surgeries
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To evaluate Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1);Secondary Objective: 1. To evaluate Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 2. To evaluate Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 3. To evaluate Overall Survival (OS) 4. To assess the safety and tolerability of study treatment;Primary end point(s): 1. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1);Timepoint(s) of evaluation of this end point: 1. Up to approximately 2 years | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 2. Duration of Response (DOR) per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) 3. Overall Survival (OS) 4. Number of participants experiencing an Adverse Event (AE) 5. Number of participants discontinuing study treatment due to an Adverse Event (AE);Timepoint(s) of evaluation of this end point: 1. Up to approximately 2 years 2. Up to approximately 2 years 3. Up to approximately 2 years 4. Up to approximately 2 years 5. Up to approximately 2 years | — |
Countries
Australia, Austria, Brazil, France, Israel, Korea, Republic of, Mexico, Norway, Spain, United Kingdom, United States
Contacts
Public ContactInvestigación clínica
Merck Sharp & Dohme de España SA
Outcome results
None listed